Summary: In the prespecified echocardiography substudy of the STEP-HFpEF Program (n=491; semaglutide 253, placebo 238), once-weekly semaglutide 2.4 mg attenuated progression of left atrial remodeling over 52 weeks, with an estimated mean difference in left atrial volume of -6.13 mL (95% CI: -9.85 to -2.41; P=0.0013). Right ventricular size and several diastolic indices also improved, while left ventricular mass and systolic function were unchanged.
PICO Summary
| Element | Detail |
|---|---|
| Population | 491 adults with obesity-related heart failure with preserved ejection fraction (HFpEF), with and without type 2 diabetes, who had paired echocardiography at randomisation and 52 weeks (43% of the 1,145 in the pooled STEP-HFpEF and STEP-HFpEF DM trials). Prespecified substudy of an international, multicentre, double-blind, randomised programme. |
| Intervention | Once-weekly subcutaneous semaglutide 2.4 mg for 52 weeks (n=253). |
| Comparison | Matching placebo on top of usual HFpEF care for 52 weeks (n=238). |
| Outcome | Primary outcome (change in left atrial volume): estimated mean difference (EMD) -6.13 mL; 95% CI -9.85 to -2.41; P=0.0013, favouring semaglutide. Right ventricular end-diastolic area EMD -1.99 cm; 95% CI -3.60 to -0.38; P=0.016. RV end-systolic area EMD -1.41 cm; 95% CI -2.42 to -0.40; P=0.0064. Diastolic indices: E-wave velocity EMD -5.63 cm/s (95% CI -9.42 to -1.84; P=0.0037); E/A ratio EMD -0.14 (95% CI -0.24 to -0.04; P=0.0075); E/e’ average EMD -0.79 (95% CI -1.60 to 0.01; P=0.05). No significant effect on left ventricular dimensions, mass, or systolic function. Greater weight loss correlated with greater LA volume reduction (P=0.033). No clinical outcomes (hospitalisation, mortality) were tested in this substudy. |
Semaglutide and cardiac structure in obesity-related HFpEF
RCT echo substudy · obesity HFpEF · 52 weeks
Over 52 weeks, semaglutide slowed adverse cardiac remodelling, significantly reducing left atrial volume versus placebo. These are imaging surrogates, not clinical endpoints.
Expert Commentary
The verdict here is that semaglutide was associated with a measurable slowing of adverse cardiac remodelling in obesity-related HFpEF, with a statistically significant reduction in left atrial volume and supportive signals across right ventricular size and diastolic filling. These findings are mechanistically coherent and align with the symptomatic benefit reported in the parent trials, lending biological plausibility to the idea that semaglutide may be disease-modifying in this phenotype rather than merely symptom-relieving. The principal limitation is that this is a prespecified imaging substudy of structural surrogates in roughly 43% of the programme, not a test of clinical endpoints; paired echocardiography was available in a self-selected subset, raising the possibility of selection effects, and reverse cardiac remodelling has an inconsistent record of translating into reductions in hospitalisation or death. The effect sizes are modest and the E/e’ result sits at the boundary of significance. The programme was funded by the manufacturer (Novo Nordisk), with several sponsor-affiliated authors, which warrants the usual caution even within a double-blind design. Can I use this with my patients? For a patient with obesity-related HFpEF already a candidate for semaglutide on symptom and weight grounds, these data are reassuring and supportive, but they should not be presented as proof of remodelling-driven outcome benefit. Confirmation against hard cardiovascular endpoints is the outstanding need.
References
Solomon SD, Ostrominski JW, Wang X, et al. Effect of semaglutide on cardiac structure and function in patients with obesity-related heart failure. J Am Coll Cardiol. 2024;84(17):1587-1602. doi:10.1016/j.jacc.2024.08.021
